Progress in Nuclear Magnetic Resonance Spectroscopy最新文献

Developments of NMR methodology to characterise the structures of molecular organic structures are reviewed, concentrating on the previous decade of research in which density functional theory-based calculations of NMR parameters in periodic solids have become widespread. With a focus on demonstrating the new structural insights provided, it is shown how “NMR crystallography” has been used in a spectrum of applications from resolving ambiguities in diffraction-derived structures (such as hydrogen atom positioning) to deriving complete structures in the absence of diffraction data. As well as comprehensively reviewing applications, the different aspects of the experimental and computational techniques used in NMR crystallography are surveyed. NMR crystallography is seen to be a rapidly maturing subject area that is increasingly appreciated by the wider crystallographic community.

A review of developments in fluorine NMR of relevance to synthesis, characterisation and industrial applications of small organic molecules. Developments considered include those in spectrometer technology, computational methods and pulse sequences. The review of 80 references outlines applications in areas of identification, quantitation, mixture analysis, reaction monitoring, environmental studies and fragment-based drug design.

Measuring accurate molecular self-diffusion coefficients, D, by nuclear magnetic resonance (NMR) techniques has become routine as hardware, software and experimental methodologies have all improved. However, the quantitative interpretation of such data remains difficult, particularly for small molecules. This review article first provides a description of, and explanation for, the failure of the Stokes-Einstein equation to accurately predict small molecule diffusion coefficients, before moving on to three broadly complementary methods for their quantitative interpretation. Two are based on power laws, but differ in the nature of the reference molecules used. The third addresses the uncertainties in the Stokes-Einstein equation directly. For all three methods, a wide range of examples are used to show the range of chemistry to which diffusion NMR can be applied, and how best to implement the different methods to obtain quantitative information from the chemical systems studied.

Motor proteins are involved in a variety of cellular processes. Their main purpose is to convert the chemical energy released during adenosine triphosphate (ATP) hydrolysis into mechanical work. In this review, solid-state Nuclear Magnetic Resonance (NMR) approaches are discussed allowing studies of structures, conformational events and dynamic features of motor proteins during a variety of enzymatic reactions. Solid-state NMR benefits from straightforward sample preparation based on sedimentation of the proteins directly into the Magic-Angle Spinning (MAS) rotor. Protein resonance assignment is the crucial and often time-limiting step in interpreting the wealth of information encoded in the NMR spectra. Herein, potentials, challenges and limitations in resonance assignment for large motor proteins are presented, focussing on both biochemical and spectroscopic approaches. This work highlights NMR tools available to study the action of the motor domain and its coupling to functional processes, as well as to identify protein-nucleotide interactions during events such as DNA replication. Arrested protein states of reaction coordinates such as ATP hydrolysis can be trapped for NMR studies by using stable, non-hydrolysable ATP analogues that mimic the physiological relevant states as accurately as possible. Recent advances in solid-state NMR techniques ranging from Dynamic Nuclear Polarization (DNP), ³¹P-based heteronuclear correlation experiments, ¹H-detected spectra at fast MAS frequencies >100 kHz to paramagnetic NMR are summarized and their applications to the bacterial DnaB helicase from Helicobacter pylori are discussed.

Sensing methodologies for the detection of target compounds in mixtures are important in many different contexts, ranging from medical diagnosis to environmental analysis and quality assessment. Ideally, such detection methods should allow for both identification and quantification of the targets, minimizing the possibility of false positives. With very few exceptions, most of the available sensing techniques rely on the selective interaction of the analyte with some detector, which in turn produces a signal as a result of the interaction. This approach hence provides indirect information on the targets, whose identity is generally ensured by comparison with known standards, if available, or by the selectivity of the sensor system itself. Pursuing a different approach, NMR chemosensing aims at generating signals directly from the analytes, in the form of a (complete) NMR spectrum. In this way, not only are the targets unequivocally identified, but it also becomes possible to identify and assign the structures of unknown species.

In this review we show how relaxation- and diffusion-based NMR techniques, assisted by appropriate nanoparticles, can be used to edit the ¹H NMR spectrum of a mixture and extract the signals of specific target compounds. Monolayer-protected nanoparticles, in particular those made from gold, are well suited to this task because they provide a versatile, protein-size support to build or incorporate supramolecular receptors. Remarkably, the self-organized and multifunctional nature of the nanoparticle coating allows exploitation of different kinds of non-covalent interactions, to provide tailored binding sites for virtually any class of molecules.

From the NMR standpoint, the reduced translational and rotational diffusion rates of bulky nanoparticles offer a way to manipulate the states of the monolayer spins and build a reservoir of magnetization that can be selectively transferred to the interacting analytes. In addition, the low correlation time and the enhanced rigidity of the coating molecules (due to their grafting and crowding on the particle surface) promote efficient spin diffusion, useful in saturation transfer experiments. The optimized combination of NMR experiments and nanoreceptors can ultimately allow the detection of relevant analytes in the micromolar concentration range, paving the way to applications in the diagnostic field and beyond.

Dynamical NMR spectroscopy provides unique mechanistic understanding of the transport and relaxation processes in glass-forming liquids over timescales typically ranging from ~10⁻⁹ s to ~10² s, and thus has been used extensively in the past to study the dynamical behavior of polymeric and organic glass-forming liquids. However, reports in the literature of similar studies on inorganic glass-forming liquids have remained somewhat limited due to the experimental challenges. In this contribution we present a review of the high-temperature NMR spectroscopic studies of atomic and molecular dynamics in a wide variety of inorganic glass-forming liquids including oxides, halides and chalcogenides as well as select ionic liquids and molten salts. The significance of these dynamical processes in understanding the nature of the liquid-to-glass transition and their connection with the macroscopic transport properties of these liquids are discussed.

NMR spectroscopy is a versatile tool for studying time-dependent processes: chemical reactions, phase transitions or macromolecular structure changes. However, time-resolved NMR is usually based on the simplest among available techniques – one-dimensional spectra serving as “snapshots” of the studied process. One of the reasons is that multidimensional experiments are very time-expensive due to costly sampling of evolution time space. In this review we summarize efforts to alleviate the problem of limited applicability of multidimensional NMR in time-resolved studies. We focus on techniques based on sparse or non-uniform sampling (NUS), which lead to experimental time reduction by omitting a significant part of the data during measurement and reconstructing it mathematically, adopting certain assumptions about the spectrum. NUS spectra are faster to acquire than conventional ones and thus better suited to the role of “snapshots”, but still suffer from non-stationarity of the signal i.e. amplitude and frequency variations within a dataset. We discuss in detail how these instabilities affect the spectra, and what are the optimal ways of sampling the non-stationary FID signal. Finally, we discuss related areas of NMR where serial experiments are exploited and how they can benefit from the same NUS-based approaches.

A major goal in structural biology is to unravel how molecular machines function in detail. To that end, solution-state NMR spectroscopy is ideally suited as it is able to study biological assemblies in a near natural environment. Based on methyl TROSY methods, it is now possible to record high-quality data on complexes that are far over 100 kDa in molecular weight. In this review, we discuss the theoretical background of methyl TROSY spectroscopy, the information that can be extracted from methyl TROSY spectra and approaches that can be used to assign methyl resonances in large complexes. In addition, we touch upon insights that have been obtained for a number of challenging biological systems, including the 20S proteasome, the RNA exosome, molecular chaperones and G-protein-coupled receptors. We anticipate that methyl TROSY methods will be increasingly important in modern structural biology approaches, where information regarding static structures is complemented with insights into conformational changes and dynamic intermolecular interactions.

NMR spectroscopy of oriented samples makes accessible residual anisotropic intramolecular NMR interactions, such as chemical shift anisotropy (RCSA), dipolar coupling (RDC), and quadrupolar coupling (RQC), while preserving high spectral resolution. In addition, in a chiral aligned environment, enantiomers of chiral molecules or enantiopic elements of prochiral compounds adopt different average orientations on the NMR timescale, and hence produce distinct NMR spectra or signals. NMR spectroscopy in chiral aligned media is a powerful analytical tool, and notably provides unique information on (pro)chirality analysis, natural isotopic fractionation, stereochemistry, as well as molecular conformation and configuration. Significant progress has been made in this area over the three last decades, particularly using polypeptide-based chiral liquid crystals (CLCs) made of organic solutions of helically chiral polymers (as PBLG) in organic solvents. This review presents an overview of NMR in polymeric LCs. In particular, we describe the theoretical tools and the major NMR methods that have been developed and applied to study (pro)chiral molecules dissolved in such oriented solvents. We also discuss the representative applications illustrating the analytical potential of this original NMR tool. This overview article is dedicated to thirty years of original contributions to the development of NMR spectroscopy in polypeptide-based chiral liquid crystals.